Testosterone and Chronic Pain

Why Testosterone Replacement Therapy (TRT) Matters for Chronic Pain Patients

Testosterone plays far more than a sexual or reproductive role. It is a critical hormone for cellular repair, pain modulation, muscle and bone maintenance, immune regulation, and central nervous system (CNS) function. Modern research shows that chronic pain patients commonly experience hormone depletion, especially testosterone deficiency, due to both the physiological stress of pain and the suppressive effects of long-term opioid therapy (Basaria, 2013; Rubinstein et al., 2019)¹².

Because testosterone influences multiple pathways involved in pain processing, cognition, and physical resilience, testing and treating testosterone deficiency should now be considered a standard component of chronic pain management.

Why Testosterone Is Essential in Chronic Pain Care

1. Pain Control & Opioid Receptor Function

Testosterone supports endogenous opioid activity and mu-opioid receptor sensitivity. Low testosterone reduces the effectiveness of both natural and prescribed opioids, leading to higher pain levels, depression, and lower treatment response (Reddy et al., 2018)³.

2. CNS Health: Mood, Motivation, and Neurochemistry

Testosterone influences:

• Dopamine and norepinephrine activity

• Mood regulation

• Cognitive clarity

• Sleep quality

Low testosterone is strongly associated with depression, low motivation, and increased pain perception—all common in chronic pain patients (Zhao et al., 2016)⁴.

3. Muscle, Bone, and Tissue Repair

Adequate testosterone levels are critical for:

• Muscle mass maintenance

• Bone density

• Tissue healing

• Exercise tolerance

Deficiency increases fracture risk and slows healing at pain or injury sites (Traish, 2021)⁵.

4. Testosterone Matters for Women Too

Testosterone is not just a “male hormone.” Women require lower—but equally important—levels for:

• Libido

• Muscle and bone health

• Cognitive function

• Pain tolerance

• Dopamine/norepinephrine activity

Testosterone deficiency impacts women with chronic pain just as significantly as it does men.

How Chronic Pain Causes Hormone Depletion

Chronic pain can dysregulate the hypothalamic-pituitary-gonadal (HPG) axis, leading to reduced production of gonadotropins (LH, FSH) and ultimately lower testosterone levels (Aloisi & Bonifazi, 2018)⁶.

Long-term severe pain can also alter CNS function through neuroplasticity, further impairing hormone signaling pathways and contributing to fatigue, mood instability, and amplified pain.

How Opioids Reduce Testosterone Levels

Opioid-induced androgen deficiency (OPIAD) is one of the most common causes of low testosterone in chronic pain patients.

Opioids suppress:

• GnRH in the hypothalamus

• LH & FSH in the pituitary

• Direct testosterone production in gonads and adrenal glands

This results in:

• Low total testosterone

• Low free testosterone

• Low estradiol (due to decreased aromatization)

• Increased fatigue, pain sensitivity, and depression (Rubinstein et al., 2019)²

Both men and women on chronic opioid therapy can experience OPIAD.

Testing for Testosterone Deficiency in Chronic Pain Patients

Tests to Order

• Morning total testosterone

• Free testosterone

• SHBG (sex hormone binding globulin)

• LH, FSH (to determine pituitary involvement)

• Estradiol

• DHEA-S

• Cortisol & thyroid panel (pain-related deficiencies often coexist)

A deficiency should be considered present when either total OR free testosterone is low.
For chronic pain, total testosterone is clinically important because protein-bound testosterone may be required for CNS transport and opioid receptor modulation.

When TRT Should Be Considered

Testosterone replacement therapy should be employed in chronic pain patients who demonstrate:

• Low total or free testosterone

• Symptoms of deficiency (fatigue, low libido, depression, weakness, poor pain control)

• History of opioid use

• Evidence of pituitary suppression

Properly monitored TRT can:

• Improve pain control

• Enhance opioid responsiveness

• Reduce fatigue and depression

• Increase physical strength and bone density

• Improve overall quality of life (Basaria, 2013; Reddy et al., 2018)¹³

Conclusion

Chronic pain is not just a musculoskeletal or neurological condition—it is a hormonal condition as well. Testosterone plays a central role in CNS function, emotional well-being, inflammation control, tissue repair, and how effectively the body responds to opioid medications.

When testosterone levels fall—whether due to severe, ongoing pain or opioid therapy—pain becomes harder to manage, healing slows, and quality of life declines.

Testing and treating testosterone deficiency is an essential, evidence-supported component of comprehensive chronic pain care.

Chronic pain patients deserve hormone-optimized treatment, not partial solutions.

References

1. Basaria, S. (2013). Androgen deficiency in chronic illness: Recognition and management. Nature Reviews Endocrinology, 9(2), 107–118.

2. Rubinstein, A. L., Carpenter, D. M., & Minkoff, J. R. (2019). Opioid-induced androgen deficiency in chronic pain patients: Prevalence and clinical impact. Pain Medicine, 20(2), 362–371.

3. Reddy, A., et al. (2018). Testosterone and endogenous opioid function: Implications for pain modulation. Journal of Pain Research, 11, 1569–1578.

4. Zhao, R., et al. (2016). Testosterone and central nervous system function: Mood, cognition, and pain perception. Frontiers in Neuroscience, 10, 62.

5. Traish, A. (2021). Testosterone’s role in bone, muscle, and tissue repair: Implications for clinical therapy. Andrology, 9(4), 1260–1272.

6. Aloisi, A. M., & Bonifazi, M. (2018). Chronic pain and the HPG axis: Stress-mediated hormonal suppression. Journal of Endocrinological Investigation, 41(5), 571–582.